Phagocyte activation has been studied using membrane potential sensitive fluorescent probe, surface charge and ultrastructural techniques in leukocytes from normal subjects and patients with abnormal phagocytes and using pharmacologic probes such as histamine and Vitamin K. The data indicate that limited secretion of specific granules, which accompanies chemotaxis, is associated with increased cell adhesiveness and increased availability of chemoattractant receptors. Limited secretion may be required for neutrophil margination in vivo. A patient with specific granule deficiency has been indentified and his neutrophils support these concepts. Studies of the two populations of neutrophils we had identified previously have been extended. Neutrophil heterogeneity of elicited changes in membrane potential to chemotactic factors have been demonstrated using the fluorescent activated cell sorter and the probe di-0-C5(3). Neutrophil function studies indicate that some "acquired defects of neutrophil function represent redistribution of neutrophil populations rather than intrinsic cell defects. In other studies of the pathogenesis of abnormal chemotaxis during pregnancy an acquired neutrophil defect with abnormal neutrophil chemoattractant receptors has been identified.